Related art can be generalized by compounds of the following structural type: ##STR1## in which n is 4 or 5 and B is a substituted or unsubstituted 2-pyrimidyl moiety. These and related compounds have been prepared as psychotropic agents and are described in:
Wu, et al., Journal of Medicinal Chemistry, 15/5, 477-479 (1972). PA1 Wu, et al., U.S. Pat. No. 3,717,634 patented Feb. 20, 1973. PA1 Wu, et al., U.S. Pat. No. 3,907,801 patented Sept. 23, 1975. PA1 Wu, et al., U.S. Pat. No. 3,976,776 patented Aug. 24, 1976. PA1 Wu, et al., U.S. Pat. No. 3,398,151 patented Aug. 20, 1968. PA1 Wu, et al., Journal of Medicinal Chemistry, 12/4, 876-881 (1969).
Anxiolytic use of one of the above compounds (n=4, B=2-pyrimidyl) which is referred to by the name buspirone, is disclosed by Casten, et al., U.S. Pat. No. 4,182,763 patented Feb. 8, 1980. Currently, clinical studies to support a submission to U.S. Food & Drug Administration for the use of buspirone in treatment of anxiety neurosis are being conducted.
Another related group of compounds, including some glutarimides but wherein the B substituent is phenyl or substituted phenyl, is disclosed in:
Of increasing dissimilarity are the compounds of the following structure disclosed by Najer, H., et al., in UK Patent Application No. 7,921,307, published as GB No. 2,023,594A on Jan. 3, 1980. ##STR2## These CNS active compounds are described as being useful in treatment of anxiety and depression.
A piperidyl compound of the following structure was reported by Pollard, et al., in The Journal of Organic Chemistry, 24/6, 764-767 (1959); but no utility was given. ##STR3##
Finally, related but not closely, are some 3,3-dialkylglutarimides as shown in the following structure and reported by Benica, et al., Journal of the American Pharmaceutical Association, 1950, 451-456. ##STR4## where R.sup.1 is C.sub.1 to C.sub.4 alkyl and R.sup.2 is H or C.sub.1 to C.sub.4 alkyl. Pharmcological testing of these glutarimides did not reveal any useful physiological activity of significance.
As described in the references cited hereinabove, buspirone has a biological profile of a clinically effective anxiolytic agent. However, in certain biological models such as .sup.3 H-spiperone binding studies and apomorphine stereotypy inhibition, buspirone gives results indicative of neuroleptic or antipsychotic activity. Consequently, an object of the instant invention has been to discover a series of more selective CNS-active compounds; i.e. compounds devoid of neuroleptic activity but which otherwise retain buspirone's novel anxiolytic profile.